Studies in this section involve patients with islet cell tumors (primarily with Zollinger-Ellison syndrome [ZES]) and are directed at further understanding the pathogenesis of the syndrome and to developing alternative, more effective modes of therapy utilizing both medical and surgical approaches. A. Control of symptoms due to hormone overproduction by tumor. Patients with ZES have islet cell tumors which release excess amounts of gastrin which causes a severe ulcer diathesis. During the year increasingly effective antisecretory drugs, such as the H+-K+ ATPase inhibitor lansoprazole, has been shown to be effective and have a prolonged duration of action. Because many of these patients require surgery and cannot take oral drugs, a simplified effective method involving parenteral use of ranitidine has been developed. Currently used drugs such as omeprazole used at recommended doses cost many patients with ZES >$10/day limiting compliance and during the year we have shown that currently recommended doses are too high and can be reduced resulting in significant financial savings without reducing efficacy. B. Tumor localization and possible surgical cure. All patients with ZES have a potentially malignant tumor yet current cure rates are <20% because of their small size. We have developed increasingly effective means of localizing these tumors including portal venous sampling, intraarterial secretin administration with hepatic venous gastrin sampling, MRI scanning and careful exploration methods of the duodenum at surgery. In collaboration with J. Norton, NCI, we have increased the immediate post-op cure rate to 60% with a 5 year cure rate of 30%.